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Biomedical subjects

V Mohan

Publications and source records attributed to V Mohan.

At least 37 records · Page 2Linked to original sources

Selenium and diabetes in the tropics.

We have examined the possibility that selenium deficiency may underlie one or more of the following peculiarities of chronic pancreatitis in tropical as compared to temperate zones: much higher prevalence, propensity for pancreatic calculi, and high frequency of diabetes. Selenium was measured by graphite furnace atomic absorption spectrometry in sera from 20 healthy volunteers, 36 patients with chronic pancreatitis (calcific 35, diabetic 32), and 23 patients with primary forms of diabetes, from Madras, South India; results were compared with data from 41 controls and 37 patients with chronic pancreatitis (calcific 13, diabetes 8) from Manchester, North West, England. We conclude that (a) bioavailability of selenium is equally high in each geographic area; (b) decrement in serum selenium (p less than 0.001) is of a similar order in Manchester and Madras patients, which denies a connection with calculi formation or pancreatic exocrine failure (since the incidence of these two problems was substantially higher in the Madras series); and (c) selenium levels do not account for accelerated course to diabetes in tropical chronic pancreatitis.

Adolescent

An analysis of amplified insulin gene products in diabetics of Indian origin.

We have previously described an increased incidence of the class 3 allele of the hypervariable region (HVR) 5' to the insulin gene in south Indian non-insulin dependent diabetics; this association is absent in Punjabi Sikhs with this disorder. Using the polymerase chain reaction we have amplified parts of the insulin gene from 130 subjects to look for mutations which may be in linkage disequilibrium with the class 3 allele and hence explain its association with non-insulin dependent diabetes (NIDDM). In 23 south Indian subjects with NIDDM, using the restriction enzyme MboII, a B chain mutant (insulin Chicago) was excluded. Two patterns (alpha and beta) were found, representing a PstI polymorphism in the 3' untranslated region of the insulin gene. In subjects homozygous for the class 1 allele, the allelic frequency for alpha was 0.94 (143/152) and for beta was 0.06, in heterozygotes (1,3) alpha 0.63 (54/86) and beta 0.37, and in homozygotes for the class 3 allele alpha 0.18 (4/22) and beta 0.82 (p less than 0.001), thus establishing linkage disequilibrium between these two loci. No differences in allelic frequency were found in the south Indians or Punjabi Sikhs between controls and the different types of non-insulin requiring diabetes (NIDDM, fibrocalculous pancreatic diabetes and maturity onset diabetes of the young) when both groups were matched for insulin genotypes. Thus, although this polymorphism in the 3' untranslated region of the insulin gene is in linkage disequilibrium with the class 3 allele, it does not appear to be any better at predicting diabetes than the class 3 allele itself.

Alleles

Microalbuminuria in NIDDM patients in south India.

Urinary albumin excretion (UAE) was estimated by radioimmunoassay in 316 non-insulin dependent diabetic patients (NIDDM), with diabetes for 10 or more years and proteinuria less than 150 mg/24 h. Albuminuria was determined in 24 h collection of urine in 259 patients but in the other 57, a random sample was used. The mean UAE was 23 +/- 45.3 (SD) micrograms/mg creatinine in the patients against 4.4 +/- 2.7 micrograms/mg in the controls (30). Ninety patients (28.5%) had microalbuminuria i.e., the UAE exceeded, 20 micrograms/mg creatinine. A higher percentage (31.7%) of men had microalbuminuria than women (23.6%). The presence of microalbuminuria was similar in the insulin-treated and in oral drug-treated patients (29.6% and 26.5% respectively). Stepwise multiple regression analysis using albumin/creatinine ratio as the dependent variable showed that factors such as blood pressure, blood glucose, HbA1, body mass index, sex, age, duration of diabetes and the association of vascular complications of diabetes did not have significant correlation to microalbuminuria. Creatinine clearance showed a significant inverse correlation to the albumin/creatinine ratio. Although the prevalence of microalbuminuria in NIDDM in this study is not significantly different from those reported from other countries, the morbidity index due to kidney disease could be high due to the large absolute number involved in our country. This underscores the need for early detection of the disease and institution of preventive measures to arrest its progression.

Adult

Spinal brucellosis.

Twenty-four cases of spinal brucellosis are described. We believe that it is possible to distinguish this condition from spinal tuberculosis on the basis of the clinical and radiological findings.

Adolescent

Plasma glucagon responses in tropical fibrocalculous pancreatic diabetes.

Plasma insulin and glucagon responses to a glucose load were measured in a group of patients with fibrocalculous pancreatic diabetes (FCPD) and compared with patients with noninsulin-dependent diabetes mellitus (NIDDM) and control subjects. Both diabetic groups had markedly diminished insulin responses but the differences between FCPD and NIDDM groups were not significant. In control subjects, in response to the glucose load, plasma glucagon levels decreased while they increased in NIDDM patients. In FCPD patients there was no significant change in glucagon levels in response to the glucose load. The study shows that FCPD patients lack pancreatic alpha-cell responses to a glucose load. This may play a role in protecting these patients against ketosis.

Adult

Fibrocalculous pancreatic diabetes and obesity.

Fibrocalculous pancreatic diabetes (FCPD) is a form of diabetes secondary to chronic pancreatitis that is found in tropical countries. Most patients with FCPD are lean and many are frankly undernourished. Four patients with FCPD who were obese are reported in this paper and this is the first report of obesity in FCPD patients.

Adult

Development of carbohydrate intolerance in offspring of Asian Indian conjugal type 2 diabetic parents.

Sixty-four offspring of conjugal diabetic parents (OCDP) who were normoglycaemic initially were available for a retest after a period of 4-9 years. Among them 10 (15.6%) had developed diabetes, 19 (29.7%) had developed IGT and the remaining 35 (54.7%) had maintained normal GTT. The predictive value of the baseline (initial) parameters was tested. Among the non-obese OCDP (BMI less than 25 and less than 27 for women and men, respectively), the initial sum of plasma glucose (sigma PG), and the mean increment of insulin during GTT (delta IRI), and the 2-h IRI values were higher in the group that developed abnormal glucose tolerance (P less than 0.05 compared to controls and normal OCDP). They also had higher insulin:glucose ratios, indicating higher insulin output for a given glucose concentration. On the other hand, among the obese OCDP the initial parameters did not differ between those who developed abnormal glucose tolerance and those who did not. Stepwise multiple regression analysis showed that the baseline sigma plasma glucose value was significantly related to the final 2-h plasma glucose when all the OCDP were taken together (P = 0.0023) and also in the non-obese OCDP (P = 0.0002). The other parameter which showed a relation to the final 2-h plasma glucose was the baseline delta IRI, although it was not statistically significant (P = 0.08). No such relation was observed in the obese group.

Blood Glucose

T-cell receptor beta-subunit gene polymorphism and autoimmune disease.

We have investigated the distribution of genotypes of a restriction fragment length polymorphism of the T-cell receptor beta-subunit gene in Caucasoid controls and patients with insulin-dependent diabetes mellitus, celiac disease, dermatitis herpetiformis, and idiopathic membranous nephropathy and also in South Indian controls and diabetics. We found no significant differences between the controls and patients with any disease in either ethnic group, a result which contrasts with previous reports of associations with both insulin-dependent diabetes mellitus and idiopathic membranous nephropathy. However, the most striking finding was a marked disparity between the genotype distribution in our Caucasoid control population and that previously reported by other investigators.

Autoimmune Diseases

Familial aggregation in type 1 (insulin-dependent) diabetes mellitus: a study from south India.

An analysis of 617 Type 1 (insulin-dependent) diabetic patients from 587 families was made. In 33 families (5.6%) there was more than one Type 1 diabetic patient. In 98 families (16.7%) positive family history of Type 2 (non-insulin-dependent) diabetes was present. There was a linear correlation between the age at diagnosis of the proband and that of the sibling (r = 0.73, p less than 0.001) in the Type 1 multiplex families. The risk of Type 1 diabetes in relatives was found to be 2.7% by Li Mantel estimate, which is lower than that reported among Europeans. The cumulative risk was higher (p less than 0.001) in the relatives of Type 1 diabetic patients with age at diagnosis less than or equal to 10 years.

Age Factors

Decreased insulin sensitivity in offspring whose parents both have type 2 diabetes.

Offspring of two Type 2 diabetic parents have a high prevalence of diabetes and impaired glucose tolerance. Studies in normoglycaemic offspring have shown abnormal insulin responses. Twenty-four non-obese offspring having normal oral glucose tolerance were investigated by the insulin tolerance test for abnormalities of insulin sensitivity. Plasma insulin responses were measured during an oral glucose tolerance test. Although the plasma glucose responses during the OGTT were similar to the control values, the corresponding insulin responses were higher. The mean area under the insulin curve was 121 +/- 29 (+/- SD) mU l-1 h in the control subjects and 203 +/- 73 mU l-1 h in the offspring (p less than 0.001). The mean KITT value in the offspring was 4.3 +/- 1.9 min-1 x 100 which was significantly lower (p less than 0.01) than the value of 6.2 +/- 2.0 min-1 x 100 in the control subjects. The results suggest that some offspring of two Type 2 diabetic parents have low insulin sensitivity and the presence of hyperinsulinism may be a compensatory phenomenon.

Adult

Combination therapy of glibenclamide and insulin in NIDDM patients with secondary failure to oral drugs.

A trial of combination therapy with glibenclamide + insulin was conducted in 26 patients with non insulin dependent diabetes mellitus (NIDDM) who had secondary failure to oral hypoglycaemic agents (OHA). Patients were included in the study if they failed to respond to a dose of 15 mg of glibenclamide under strict dietary regulations. Small doses of insulin were added until satisfactory glucoregulation was achieved. On withdrawal of the OHA, in 20 patients, the post-prandial plasma glucose values (PPBS) increased again by greater than or equal to 25%; they were considered as "responders". Responders were divided into two equal groups of alternate patients; group I was treated with insulin + glibenclamide and group II with insulin + placebo. The patients were then followed up at monthly intervals for 6 months. The dose of insulin required to maintain normal plasma glucose value was significantly lower (P less than 0.05) in group I. Fewer patients in group I needed two injections of insulin per day; however this difference was not statistically significant. Normalisation of serum triglyceride and lowering of HbA1 occurred in both groups. This study shows that addition of glibenclamide to insulin treatment is advantageous in NIDDM patients showing secondary failure to OHA.

Administration, Oral

Changes in peripheral insulin concentrations in non insulin dependent diabetes during treatment. Assessment by mathematical applications.

Serum immunoreactive insulin responses to meal stimulus were studied in 20 newly detected non insulin dependent diabetes mellitus patients, following one week of treatment with high carbohydrate, high fibre diet and glibenclamide. Ten patients showed "rapid glycaemic response" i.e. the glycaemic response was good within a week. The rest of them were called "slow responders". The insulin responses were heterogenous. Mathematical calculations using the glucose and insulin responses showed improved beta cell function and peripheral action of insulin in rapid responders. On the other hand, the slow responders showed only slightly improved beta cell function with no change in peripheral action of insulin. The second phase of the study constituted follow-up studies upto 6 months. The corrected insulin response (CIR) increased initially in several patients. The peripheral insulin action improved in all patients with longer duration of treatment and lower insulin concentrations were required to maintain normoglycaemia at this stage. The results of the study indicate that a) multiple factors influence glucoregulation, b) even short term effects of the drug appear to be mediated by extra pancreatic mechanisms, and c) the extrapancreatic action improves significantly on long term use of the drug.

Adult

Comparative study of monocomponent insulins and conventional insulins on the course of diabetic nephropathy. A follow-up study.

Two matched groups of insulin requiring non-insulin dependent diabetic (NIDDM) patients with mild proteinuria (200 to 999 mg/day), one on mono component (MC) insulin therapy and the other on conventional insulins were studied for a 3 year period to evaluate the course of nephropathy in these two groups. Twenty-seven and 35 patients were followed-up in the MC insulin and conventional insulin groups respectively. In the MC insulin treated group, the percentage of patients showing deterioration in proteinuria was lower (11% vs 34%, P less than 0.05) and the percentage showing improvement was higher (48% vs 29%) compared to the conventional insulin treated group. Insulin antibody titres decreased significantly in the MC insulin group and serum C-peptide values decreased in both groups on follow-up.

Diabetes Mellitus, Type 2

Abnormalities in insulin response to intravenous glucose in offspring of conjugal (type 2) diabetic parents.

Glucose and insulin responses were measured during intravenous glucose tolerance test in 12 normal controls and 16 normoglycaemic adult offspring of conjugal diabetic parents. The glucose response curve and the glucose disposal rate in the offspring were not different from the normal pattern. These subjects elicited a lower first phase insulin (0-10 minutes area under the curve, p = 0.04), lower peak immunoreactive insulin response (p = 0.032) and also showed a delay in the first phase (p = 0.037) compared to control values. The second phase of insulin (11-120 minutes area) was not significantly different in the two groups. These changes could serve as early markers of diabetes in offspring of conjugal diabetic parents.

Adult

Immunoreactive insulin and insulin degrading enzymes in erythrocytes. A preliminary report.

Immunoreactive insulin (IRI) and insulin degrading enzyme activity (IDEA) of the plasma and the corresponding erythrocyte lysate were estimated in 21 normal volunteers, 18 non insulin dependent diabetic patients (NIDDM), and 16 insulin dependent diabetics (IDDM). The erythrocytes contained several-fold higher concentrations of IRI than in plasma, both in normal and diabetic subjects. The values in controls ranged from 80 to 458 uU/ml against a range of 5 to 25 uU/ml in the corresponding plasma samples. The IRI contents of the diabetic patients were also similar. It showed no correlation to the fasting plasma glucose or the plasma IRI. Following an oral glucose load, no change occurred in the IRI content of the erythrocytes, unlike the changes seen in plasma. The IRI content of the lysate increased with dilution of the sample. The IDEA was higher in diabetic patients compared to controls, especially so in the IDDM (P less than 0.01). It also showed more than one peak activity at different pH of the reaction buffer, indicating the possibility of a complex of enzymes. Human erythrocytes contain large pools of IRI and its degrading enzymes. The significance of the pool of the insulin in non-target tissue needs to be studied.

Adult

Evidence for induction of cytochrome P-450I in patients with tropical chronic pancreatitis.

Theophylline kinetics, as an in vivo probe for the potentially toxic cytochrome P-450I pathway of drug metabolism, were studied in 11 healthy volunteers and 11 patients with calcific chronic pancreatitis at Madras, South India. Theophylline clearance was faster in the patients than controls [median 69 (range 39-114) vs 45 (33-56) ml h-1 kg-1, p = 0.003]. In keeping with this finding, detailed social histories identified a higher exposure level in the patients to xenobiotics that are inducers of cytochrome P-450I and/or yield reactive metabolites upon processing thereby (score 7, 4-11 vs 3, 2-9, p = 0.002). However, the concentration of D-glucaric acid in urine, as a marker of phase II conjugating pathways of drug metabolism, was similar in patients and controls. This pattern of drug metabolism could predispose to oxidant stress: hence micronutrient antioxidant supplements may have therapeutic (or even prophylactic) value in tropical chronic pancreatitis.

Adolescent